Vascular endothelial growth factor (VEGF) has long been recognized as a hypotensive mediator. Little is known regarding the contribution of polymorphisms in VEGF gene to essential hypertension (EH), however. We aimed to investigate the association between +405 VEGF C/G single nucleotide polymorphism (SNP) and occurrence of EH in a sample of patients with diabetes. A study population of 474 subjects with diabetes of which 45.6% (216) had EH was enrolled in this study. Interviews and physical examinations were performed in a clinical setting. Subjects were matched in baseline anthropometric and biochemical characteristics except for total cholesterol. Genotyping of +405 VEGF C/G (rs2010963) SNP was carried out using polymerase chain reaction–restriction fragment length polymorphism. The allelic distribution of the sample did not violate Hardy–Weinberg equilibrium. Subjects with EH had a higher frequency of G allele (P = 0.005). Additionally, those with EH had a significantly higher frequency of GG genotype (P = 0.015). In multivariate logistic regression models controlling for possible confounders, having GG against CC genotype was associated with an odds ratio of 2.51 (95% CI: 1.44–4.38; P = 0.001). Moreover, presence of each G allele was linked to a 1.58-fold increase in risk of having EH (95% CI: 1.200–2.086; P = 0.001). In conclusion, +405 VEGF C/G SNP is associated with EH in patients with diabetes, suggesting presence of G allele and GG or CG genotype confer susceptibility towards EH.
Essential hypertension Single nucleotide polymorphism Vascular endothelial growth factor
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We wish to thank all medical and nursing team of Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital for collaboration in this project.
Conflict of interest
The authors declare that they have no conflicts of interest.
Vincenti V, Cassano C, Rocchi M, Persico G (1996) Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation 93:1493–1495PubMedGoogle Scholar
Lin TH, Su HM, Wang CL et al (2010) Vascular endothelial growth factor polymorphisms and extent of coronary atherosclerosis in Chinese population with advanced coronary artery disease. Am J Hypertens 23:960–966PubMedCrossRefGoogle Scholar
Palmirotta R, Ferroni P, Ludovici G et al (2010) VEGF-A gene promoter polymorphisms and microvascular complications in patients with essential hypertension. Clin Biochem 43:1090–1095PubMedCrossRefGoogle Scholar
Awata T, Inoue K, Kurihara S et al (2002) A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51:1635–1639PubMedCrossRefGoogle Scholar
Howell WM, Ali S, Rose-Zerilli MJ, Ye S (2005) VEGF polymorphisms and severity of atherosclerosis. J Med Genet 42:485–490PubMedCrossRefGoogle Scholar
Sandrim VC, Palei AC, Cavalli RC et al (2009) Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension. Mol Hum Reprod 15:115–120PubMedCrossRefGoogle Scholar
American Diabetes Association (2005) Diagnosis and classification of diabetes mellitus. Diabetes Care 28:S37–S42CrossRefGoogle Scholar
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMedGoogle Scholar
Esteghamati A, Mansournia N, Nakhjavani M, et al (2011) Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes. Mol Biol Rep 2011 Jul 10. [Epub ahead of print]Google Scholar
Plouet J, Schilling J, Gospodarowicz D (1989) Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 8:3801–3806PubMedGoogle Scholar
Senger DR, Galli SJ, Dvorak AM et al (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985PubMedCrossRefGoogle Scholar
Weis SM, Cheresh DA (2005) Pathophysiological consequences of VEGF-induced vascular permeability. Nature 437:497–504PubMedCrossRefGoogle Scholar
Gyurkovics M, Lohinai Z, Gyorfi A et al (2009) Venodilatory effect of vascular endothelial growth factor on rat gingiva. J Periodontol 80:1518–1523PubMedCrossRefGoogle Scholar
Wongpiyabovorn J, Hirankarn N, Ruchusatsawat K et al (2011) The association of single nucleotide polymorphism within vascular endothelial growth factor gene with systemic lupus erythematosus and lupus nephritis. Int J Immunogenet 38:63–67PubMedCrossRefGoogle Scholar
Lin TH, Wang CL, Su HM et al (2010) Functional vascular endothelial growth factor gene polymorphisms and diabetes: effect on coronary collaterals in patients with significant coronary artery disease. Clin Chim Acta 411:1688–1693PubMedCrossRefGoogle Scholar
van der Meer P, De Boer RA, White HL et al (2005) The VEGF +405 CC promoter polymorphism is associated with an impaired prognosis in patients with chronic heart failure: a MERIT-HF substudy. J Card Fail 11:279–284PubMedCrossRefGoogle Scholar
Nikzamir A, Esteghamati A, Hammedian AA, Mahmoudi T (2011) The role of vascular endothelial growth factor +405 G/C polymorphism and albuminuria in patients with type 2 diabetes mellitus. Mol Biol Rep 2011 May 12. [Epub ahead of print]Google Scholar
Young HS, Summers AM, Bhushan M et al (2004) Single-nucleotide polymorphisms of vascular endothelial growth factor in psoriasis of early onset. J Invest Dermatol 122:209–215PubMedCrossRefGoogle Scholar
Han SW, Kim GW, Seo JS et al (2004) VEGF gene polymorphisms and susceptibility to rheumatoid arthritis. Rheumatology (Oxf) 43:1173–1177CrossRefGoogle Scholar
Salvarani C, Boiardi L, Casali B et al (2004) Vascular endothelial growth factor gene polymorphisms in Behçet’s disease. J Rheumatol 31:1785–1789PubMedGoogle Scholar
Boiardi L, Casali B, Nicoli D et al (2003) Vascular endothelial growth factor gene polymorphisms in giant cell arteritis. J Rheumatol 30:2160–2164PubMedGoogle Scholar